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Design, synthesis, structure, in vitro cytotoxic activity evaluation and docking studies on target enzyme GSK-3β of new indirubin-3'-oxime derivatives
- Source :
- Scientific Reports, Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
- Publication Year :
- 2020
-
Abstract
- The addition of chalcone and amine components into indirubin-3′-oxime resulted in 15 new derivatives with high yields. Structures of new derivatives were also elucidated through 1D, 2D-NMR and HR-MS(ESI) spectra and X-ray crystallography. All designed compounds were screened for cytotoxic activity against four human cancer cell lines (HepG2, LU-1, SW480 and HL-60) and one human normal kidney cell line (HEK-293). Compound 6f exhibited the most marked cytotoxicity meanwhile cytotoxicity of compounds 6e, 6h and 6l was more profound toward cancer cell lines than toward normal cell. These new derivatives were further analyzed via molecular docking studies on GSK-3β enzyme. Docking analysis shows that most of the derivatives exhibited potential inhibition activity against GSK-3β with characteristic interacting residues in the binding site. The fast pulling of ligand scheme was then employed to refine the binding affinity and mechanism between ligands and GSK-3β enzyme. The computational results are expected to contribute to predicting enzyme target of the trial inhibitors and their possible interaction, from which the design of new cytotoxic agents could be created in the future.
- Subjects :
- Chalcone
Spectrometry, Mass, Electrospray Ionization
Indoles
Magnetic Resonance Spectroscopy
Stereochemistry
Cell Survival
lcsh:Medicine
Antineoplastic Agents
HL-60 Cells
010402 general chemistry
Crystallography, X-Ray
Ligands
01 natural sciences
Mass Spectrometry
Article
chemistry.chemical_compound
Inhibitory Concentration 50
Chalcones
Protein Domains
Catalytic Domain
Oximes
Humans
Binding site
Cytotoxicity
lcsh:Science
Analytical biochemistry
chemistry.chemical_classification
Multidisciplinary
Glycogen Synthase Kinase 3 beta
010405 organic chemistry
Chemistry
lcsh:R
Computational Biology
Hep G2 Cells
Ligand (biochemistry)
Oxime
0104 chemical sciences
Computational biology and bioinformatics
Molecular Docking Simulation
Enzyme
HEK293 Cells
Docking (molecular)
Drug Design
lcsh:Q
Indirubin
Protein Binding
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 10
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific reports
- Accession number :
- edsair.doi.dedup.....5649e27fbb2e3248f9ffd7a0e91265b9